Palladium-Catalyzed Late-Stage Functionalization of Natural Antitumor Drug: Synthesis and Bioactivity of 5-Aryl Camptothecins.

IF 3.6 2区生物学 Q2 CHEMISTRY, MEDICINAL Journal of Natural Products Pub Date : 2025-03-28 Epub Date: 2025-03-07 DOI:10.1021/acs.jnatprod.4c01344

Lian Sun, Xiao-Long Li, Qiu-Shan Huang, Wan-Sheng Ji, Xiaohuan Li, Jin-Bu Xu, Feng Gao

{"title":"Palladium-Catalyzed Late-Stage Functionalization of Natural Antitumor Drug: Synthesis and Bioactivity of 5-Aryl Camptothecins.","authors":"Lian Sun, Xiao-Long Li, Qiu-Shan Huang, Wan-Sheng Ji, Xiaohuan Li, Jin-Bu Xu, Feng Gao","doi":"10.1021/acs.jnatprod.4c01344","DOIUrl":null,"url":null,"abstract":"Camptothecin (CPT) and its derivatives have garnered significant interest due to their potent anticancer activity. In this study, 62 novel CPT derivatives (1a-31a and 1b-31b) were designed and synthesized through Pd-catalyzed late-stage modification at the C-5 position. The anticancer efficacy of these compounds against three human cancer cell lines was evaluated. Compounds 5R-12a (IC50 = 0.05 ± 0.01 μM against HCT-116) and 5R-6a (IC50 = 0.04 ± 0.03 μM against MCF-7) exhibited enhanced antitumor activity when compared to CPT. The preliminary mechanism of apoptosis was investigated through cell viability assays, protein expression, and docking analysis. The results indicated that compounds 12a and 6a exhibited a greater ability to induce apoptosis and G2/M phase arrest than did CPT. Docking results provided a possible explanation for the superior activity of the 5R configuration. This work would offer new insights for CPT lead compound development.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"706-714"},"PeriodicalIF":3.6000,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Natural Products ","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1021/acs.jnatprod.4c01344","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/7 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}

引用次数: 0

Abstract

Camptothecin (CPT) and its derivatives have garnered significant interest due to their potent anticancer activity. In this study, 62 novel CPT derivatives (1a-31a and 1b-31b) were designed and synthesized through Pd-catalyzed late-stage modification at the C-5 position. The anticancer efficacy of these compounds against three human cancer cell lines was evaluated. Compounds 5R-12a (IC₅₀ = 0.05 ± 0.01 μM against HCT-116) and 5R-6a (IC₅₀ = 0.04 ± 0.03 μM against MCF-7) exhibited enhanced antitumor activity when compared to CPT. The preliminary mechanism of apoptosis was investigated through cell viability assays, protein expression, and docking analysis. The results indicated that compounds 12a and 6a exhibited a greater ability to induce apoptosis and G2/M phase arrest than did CPT. Docking results provided a possible explanation for the superior activity of the 5R configuration. This work would offer new insights for CPT lead compound development.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

钯催化天然抗肿瘤药物的后期功能化：5-芳基喜树碱的合成和生物活性。

喜树碱（CPT）及其衍生物因其有效的抗癌活性而引起了人们的极大兴趣。本研究通过pd催化的C-5位点后期修饰，设计合成了62个新型CPT衍生物（1a-31a和1b-31b）。评价了这些化合物对三种人类癌细胞系的抗癌作用。化合物5R-12a（对HCT-116的IC50 = 0.05±0.01 μM）和5R-6a（对MCF-7的IC50 = 0.04±0.03 μM）的抗肿瘤活性较CPT增强。通过细胞活力测定、蛋白表达和对接分析初步探讨细胞凋亡机制。结果表明，化合物12a和6a比CPT具有更强的诱导细胞凋亡和G2/M期阻滞的能力。对接结果为5R结构的优越活性提供了可能的解释。这项工作将为CPT先导化合物的开发提供新的思路。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.